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https://www.readbyqxmd.com/read/28654915/inhibition-of-fak-kinase-activity-preferentially-targets-cancer-stem-cells
#1
Vihren N Kolev, Winnie F Tam, Quentin G Wright, Sean P McDermott, Christian M Vidal, Irina M Shapiro, Qunli Xu, Max S Wicha, Jonathan A Pachter, David T Weaver
Because cancer stem cells (CSCs) have been implicated in chemo-resistance, metastasis and tumor recurrence, therapeutic targeting of CSCs holds promise to address these clinical challenges to cancer treatment. VS-4718 and VS-6063 are potent inhibitors of focal adhesion kinase (FAK), a non-receptor tyrosine kinase that mediates cell signals transmitted by integrins and growth factor receptors. We report here that inhibition of FAK kinase activity by VS-4718 or VS-6063 preferentially targets CSCs, as demonstrated by a panel of orthogonal CSC assays in cell line models and surgically resected primary breast tumor specimens cultured ex vivo...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28653813/eplerenone-for-chronic-central-serous-chorioretinopathy-a-randomized-controlled-prospective-study
#2
Roy Schwartz, Zohar Habot-Wilner, Michael R Martinez, Amir Nutman, Dafna Goldenberg, Shai Cohen, Shiri Shulman, Hanan Guzner-Gur, Anat Loewenstein, Michaella Goldstein
PURPOSE: To evaluate the efficacy and safety of eplerenone for chronic nonresolving central serous chorioretinopathy (CSC). METHODS: Prospective, double-blind, randomized placebo-controlled study. Nineteen eyes of 17 patients with persistent subretinal fluid (SRF) due to CSC were enrolled and randomized to receive eplerenone 50 mg/day or placebo for 3 months, followed by a 3-month follow-up. The main outcome measure was change in SRF from baseline to 3 months of treatment...
June 27, 2017: Acta Ophthalmologica
https://www.readbyqxmd.com/read/28652251/hypoxia-induced-downregulation-of-dusp-2-phosphatase-drives-colon-cancer-stemness
#3
Pei-Chi Hou, Yo-Hua Li, Shih-Chieh Lin, Shao-Chieh Lin, Jenq-Chang Lee, Bo-Wen Lin, Jing-Ping Liou, Jang-Yang Chang, Ching-Chuan Kuo, Yi-Min Liu, H Sunny Sun, Shaw-Jenq Tsai
Cancer stem-like cells (CSC) evolve to overcome the pressures of reduced oxygen, nutrients or chemically induced cell death, but the mechanisms driving this evolution are incompletely understood. Here we report that hypoxia-mediated downregulation of the dual specificity phosphatase 2 (DUSP2) is critical for the accumulation of CSC in colorectal cancer. Reduced expression of DUSP2 led to overproduction of cyclooxygenase-2 (COX-2)-derived prostaglandin E2, which promoted cancer stemness via the EP2/EP4 signaling pathways...
June 26, 2017: Cancer Research
https://www.readbyqxmd.com/read/28651932/tmprss4-promotes-cancer-stem-cell-traits-by-regulating-cldn1-in-hepatocellular-carcinoma
#4
Shaya Mahati, Dilinaer Bolati, Ying Yang, Rui Mao, Hua Zhang, YongXing Bao
Encouraging advances in the treatment of hepatocellular carcinoma(HCC) have been achieved; however, a considerable part of patients still relapse or metastasize after therapy, and the underlying mechanisms have not been clarified yet. Here, we found that CLDN1 was markedly up-regulated in HCC tissues, and correlated with poor prognosis. Overexpression of CLDN1 dramatically promoted the capability of tumorsphere formation and cancer stem cell (CSC) traits. Furthermore, we found that TMPRSS4 was up-regulated in HCC tissues and there was a positive correlation between TMPRSS4 and CLDN1...
June 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28651817/angiogenesis-and-cancer-stem-cells-new-perspectives-on-therapy-of-ovarian-cancer
#5
REVIEW
Anna Markowska, Stefan Sajdak, Janina Markowska, Adam Huczyński
Failure in ovarian cancer therapy, following cytoreduction and chemotherapy, is related to the presence of cancer stem cells - a small subpopulation of cells resistant to chemotherapy and irradiation - in the tumour which may cause cancer relapse and manifestation of metastases. Therapies targeted at Cancer Stem Cells (CSCs), such as those employing metformin (a drug used in the treatment of diabetes type II) and salinomycin, an antibiotic isolated from Streptococcus albus bacteria, seem promising. Anti-angiogenic therapy with bevacizumab was found to be effective in all phases of ovarian cancer treatment...
June 20, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28649130/dopamine-d2-receptor-antagonist-sulpiride-enhances-dexamethasone-responses-in-the-treatment-of-drug-resistant-and-metastatic-breast-cancer
#6
Jian Li, Qing-Yu Yao, Jun-Sheng Xue, Li-Jie Wang, Yin Yuan, Xiu-Yun Tian, Hong Su, Si-Yuan Wang, Wen-Jun Chen, Wei Lu, Tian-Yan Zhou
Recent evidence shows that dopamine D2-like receptor (D2DR) antagonists, such as trifluoperazine and thioridazine, are effective for cancer therapy and inhibition of cancer stem-like cells (CSCs). In this study, we investigated the anti-cancer effects of combination therapy of dexamethasone (DEX) and sulpiride (SUL), an atypical antipsychotic, against drug-resistant and metastatic breast cancers and further explored the underlying mechanisms. Oral administration of SUL (25, 100 mg·kg(-1)·d(-1)) alone did not inhibit the tumor growth in human breast cancer MCF-7/Adr xenograft model, but dose-dependently decreased the proportion of CSCs in vitro and in vivo...
June 26, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28648376/sam68-allows-selective-targeting-of-human-cancer-stem-cells
#7
Yannick D Benoit, Ryan R Mitchell, Ruth M Risueño, Luca Orlando, Borko Tanasijevic, Allison L Boyd, Lili Aslostovar, Kyle R Salci, Zoya Shapovalova, Jennifer Russell, Masakatsu Eguchi, Diana Golubeva, Monica Graham, Anargyros Xenocostas, Michael R Trus, Ronan Foley, Brian Leber, Tony J Collins, Mickie Bhatia
Targeting of human cancer stem cells (CSCs) requires the identification of vulnerabilities unique to CSCs versus healthy resident stem cells (SCs). Unfortunately, dysregulated pathways that support transformed CSCs, such as Wnt/β-catenin signaling, are also critical regulators of healthy SCs. Using the ICG-001 and CWP family of small molecules, we reveal Sam68 as a previously unappreciated modulator of Wnt/β-catenin signaling within CSCs. Disruption of CBP-β-catenin interaction via ICG-001/CWP induces the formation of a Sam68-CBP complex in CSCs that alters Wnt signaling toward apoptosis and differentiation induction...
June 21, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28647567/stearoyl-coa-desaturase-regulates-sorafenib-resistance-via-modulation-of-er-stress-induced-differentiation
#8
Mark Kin Fai Ma, Eunice Yuen Ting Lau, Doris Hoi Wing Leung, Jessica Lo, Nicole Pui Yu Ho, Lily Kwan Wai Cheng, Stephanie Ma, Chi Ho Lin, John A Copland, Jin Ding, Regina Cheuk Lam Lo, Irene Oi Lin Ng, Terence Kin Wah Lee
We investigated the functional role and clinical significance of Stearoyl CoA desaturase-1 (SCD1) mediated endoplasmic reticulum (ER) stress in regulation of liver tumor-initiating cells (T-ICs) and sorafenib resistance, aiming to develop a novel therapeutic strategy against hepatocellular carcinomas (HCCs) METHODS We evaluated the clinic-pathological relevance of SCD1 and its correlation with sorafenib resistance in large cohorts of HCC clinical samples by qPCR and immunohistochemical analyses. Lentiviral-based overexpression and knockdown approaches were performed to characterize functional roles of SCD1 in regulation of liver T-ICs and sorafenib resistance...
June 21, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28646805/natural-cancer-therapy-and-prevention-targeted-on-cancer-cells-and-cancer-stem-cells-based-on-the-cytochrome-p45o-enzyme-cyp1b1-a-commentary
#9
William R Ware
The importance of the P450 enzyme CYP1B1 in both cancer therapy and prevention are reviewed and evidence is discussed, which provides strong biological plausibility for the therapeutic merits of this approach. The significant resistance to chemotherapy among common cancers, and the realization that in many cases chemotherapy leaves behind drug-resistant cancer cells that eventually cause recurrence and metastatic disease, has recently prompted the search for natural compounds that would circumvent this problem...
June 23, 2017: Alternative Therapies in Health and Medicine
https://www.readbyqxmd.com/read/28645561/boris-up-regulates-oct4-via-histone-methylation-to-promote-cancer-stem-cell-like-properties-in-human-liver-cancer-cells
#10
Qiuying Liu, Kefei Chen, Zhongjian Liu, Yuan Huang, Rongce Zhao, Ling Wei, Xiaoqin Yu, Jingyang He, Jun Liu, Jianguo Qi, Yang Qin, Bo Li
Accumulating evidence has revealed the importance of cancer stem cells (CSCs) in chemoresistance and recurrence. BORIS, a testes-specific CTCF paralog, has been shown to be associated with stemness traits of embryonic cancer cells and epithelial CSCs. We previously reported that BORIS is correlated with the expression of the CSC marker CD90 in hepatocellular carcinoma (HCC). These results encourage us to wonder whether BORIS exerts functions on CSC-like traits of human liver cancer cells. Here, we report that BORIS was enriched in HCC tissues...
June 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28644558/current-understanding-of-cancer-stem-cells-review-of-their-radiobiology-and-role-in-head-and-neck-cancers
#11
REVIEW
Paul Ambrose Reid, Puthenparampil Wilson, Yanrui Li, Loredana Gabriela Marcu, Eva Bezak
Evidence of cancer cells that bear attributes analogous to those of normal stem cells has developed a hierarchical model of cancer's architecture and progression. This subset of cancer stem cells (CSCs) drives the progression and therapy resistance of cancers. Research to identify the phenotypes of these CSCs presents evidence of a subpopulation that is more resistant to therapy and may proliferate in response. Literature shows that CSCs typically represent around 1%-10% of cell populations in head and neck cancer but this proportion may increase in response to a therapeutic radiation dose...
June 23, 2017: Head & Neck
https://www.readbyqxmd.com/read/28643230/crosstalk-between-m2-macrophages-and-glioma-stem-cells
#12
Leora M Nusblat, Molly J Carroll, Charles M Roth
PURPOSE: Given its extremely poor prognosis, there is a pressing need for an improved understanding of the biology of glioblastoma multiforme (GBM), including the roles of tumor subpopulations that may contribute to their growth rate and therapy resistance. The most malignant phenotypes of GBM have been ascribed to the presence of subpopulations of cancer stem cells (CSCs), which are resistant to chemotherapeutic drugs and ionizing radiation and which promote invasiveness and metastasis...
June 22, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28643126/cancer-stem-cells-in-hepatocellular-carcinoma
#13
REVIEW
Tamer Yagci, Metin Cetin, Pelin Balcik Ercin
BACKGROUND: Hepatocellular carcinoma is one of the most common cancers and the second leading cause of cancer-related deaths worldwide. Only a small proportion of patients benefit from curative treatment and the prognosis is very poor for the majority of cases due to late presentation, resistance to chemotherapy and high recurrence rate. In recent years, progress in stem cell biology allowed us to explain that hierarchically organized cancer stem cells (CSCs) drive histological and functional heterogeneity of hematological malignancies and solid tumors...
June 23, 2017: Journal of Gastrointestinal Cancer
https://www.readbyqxmd.com/read/28642170/lncrna-dancr-promotes-tumor-progression-and-cancer-stemness-features-in-osteosarcoma-by-upregulating-axl-via-mir-33a-5p-inhibition
#14
Nian Jiang, Xuedi Wang, Xianbiao Xie, Yan Liao, Ni Liu, Junfeng Liu, Nabo Miao, Jingnan Shen, Tingsheng Peng
lncRNAs regulate the initiation and progression of osteosarcoma, although the mechanism by which this occurs remains unknown. The present study shows that over-expression of the lncRNA DANCR increased osteosarcoma cell proliferation, migration, and invasion in vitro, as well as promoted xenograft tumor growth and lung metastasis in vivo. Mechanistically, DANCR promoted osteosarcoma progression by mediating cancer stem cells (CSC) features. Moreover, pull-down assays and luciferase reporter assays indicated that DANCR upregulated expression of the receptor tyrosine kinase AXL by competitively binding to miR-33a-5p...
June 19, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28641225/investigation-of-dissociation-constants-for-individual-and-total-naphthenic-acids-species-using-ultra-performance-liquid-chromatography-ion-mobility-time-of-flight-mass-spectrometry-analysis
#15
Rongfu Huang, Pamela Chelme-Ayala, Yanyan Zhang, Mohamed Changalov, Mohamed Gamal El-Din
Ultra-performance liquid chromatography ion mobility time-of-flight mass spectrometry (UPLC-IM-TOFMS) was utilized for the analysis of naphthenic acids (NAs) in fractions of pH-dependent sequential liquid-liquid extractions from oil sands process-affected water. Ion-mobility separation technique allowed the differentiation of OyS-NAs (2 ≤ y ≤ 4) from Ox-NAs (2 ≤ x ≤ 5) via drift time versus retention time separations. The results indicated that the addition of S atom to the O2-NA molecule led to a lower increase in the dissociation constant (pKa) compared to that caused by the addition of O atom...
June 18, 2017: Chemosphere
https://www.readbyqxmd.com/read/28634582/cancer-stem-cells-in-moderately-differentiated-lip-squamous-cell-carcinoma-express-components-of-the-renin-angiotensin-system
#16
Rachna S Ram, Helen D Brasch, Jonathan C Dunne, Paul F Davis, Swee T Tan, Tinte Itinteang
AIM: We investigated the expression of the renin-angiotensin system (RAS) by cancer stem cell (CSC) subpopulations we have identified in moderately differentiated lip squamous cell carcinoma (MDLSCC). METHOD: Ten MDLSCC samples underwent 3,3-diaminobenzidine (DAB) and immunofluorescent immunohistochemical (IHC) staining for (pro)renin receptor (PRR), angiotensin-converting enzyme (ACE), angiotensin II receptor 1 (ATIIR1), and receptor 2 (ATIIR2). NanoString analysis and Western blotting (WB) were performed on six MDLSCC samples for gene and protein expression, respectively...
2017: Frontiers in Surgery
https://www.readbyqxmd.com/read/28633632/antagonizing-mir-455-3p-inhibits-chemoresistance-and-aggressiveness-in-esophageal-squamous-cell-carcinoma
#17
Aibin Liu, Jinrong Zhu, Geyan Wu, Lixue Cao, Zhanyao Tan, Shuxia Zhang, Lili Jiang, Jueheng Wu, Mengfeng Li, Libing Song, Jun Li
BACKGROUND: The plasticity of cancer stem cells (CSCs)/tumor-initiating cells (T-ICs) suggests that multiple CSC/T-IC subpopulations exist within a tumor and that multiple oncogenic pathways collaborate to maintain the CSC/T-IC state. Here, we aimed to identify potential therapeutic targets that concomitantly regulate multiple T-IC subpopulations and CSC/T-IC-associated pathways. METHODS: A chemoresistant patient-derived xenograft (PDX) model of human esophageal squamous cell carcinoma (ESCC) was employed to identify microRNAs that contribute to ESCC aggressiveness...
June 21, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28633106/selective-photocytotoxicity-of-anthrols-on-cancer-stem-like-cells-the-effect-of-quinone-methides-or-reactive-oxygen-species
#18
Lidija Uzelac, Đani Škalamera, Kata Mlinarić-Majerski, Nikola Basarić, Marijeta Kralj
Cancer stem cells (CSCs) are a subpopulation of cancer cells that share properties of embryonic stem cells like pluripotency and self-renewal and show increased resistance to chemo- and radiotherapy. Targeting CSC, rather than cancer cells in general, is a novel and promising strategy for cancer treatment. Novel therapeutic approaches, such as photodynamic therapy (PDT) have been investigated. A promising group of phototherapeutic agents are reactive intermediates - quinone methides (QMs). This study describes preparation of QM precursor, 2-hydroxy-3-hydroxymethylanthracene (2) and a detailed photochemical and photobiological investigation on similar anthracene derivatives 3 and 4...
June 3, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28629854/inhibition-of-organic-anion-transporter-oat-activity-by-cigarette-smoke-condensate
#19
Katia Sayyed, Marc Le Vee, Ziad Abdel-Razzak, Olivier Fardel
Cigarette smoke condensate (CSC) has previously been shown to impair activity and expression of hepatic drug transporters. In the present study, we provided evidence that CSC also hinders activity of organic anion transporters (OATs), notably expressed at the kidney level. CSC thus cis-inhibited OAT substrate uptake in OAT1- and OAT3-transfected HEK293 cells, in a concentration-dependent manner (IC50=72.1μg/mL for OAT1 inhibition and IC50=27.3μg/mL for OAT3 inhibition). By contrast, OAT4 as well as the renal organic cation transporter (OCT) 2 were less sensitive to the inhibitory effect of CSC (IC50=351...
June 16, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28627972/immunomodulatory-effects-of-cigarette-smoke-condensate-in-mouse-macrophage-cell-line
#20
Junwei Zhao, Xiang Li, Fuwei Xie, Zhihua Yang, Xiujie Pan, Maoxiang Zhu, Pingping Shang, Cong Nie, Huimin Liu, Jianping Xie
Increasing evidence has demonstrated that the secretion of cytokines may be associated with cigarette smoke-induced immunomodulatory effects, but a comprehensive analysis of the cytokine profile for cigarette smoke condensate (CSC) exposure is lacking. The aims of this study were to (1) examine the release of 20 cytokines induced by CSC from 12 brands of cigarettes in macrophages cells (Ana-1) and (2) to investigate the general characteristics of the immunomodulatory effects of CSC. Luminex technology was used to simultaneously determine the levels of 20 cytokines (interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ (IFN-γ), keratinocyte-derived Chemokine (KC), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1α (MIP-1α), induced protein 10 (IP-10), tumor necrosis factor α (TNF-α), vascular endothelial growth factor (VEGF), monkine inducible by γ interferon (MIG), and fibroblast growth factor (FGF)-basic) in the supernatants from Ana-1 cells treated with the CSC...
June 1, 2017: International Journal of Immunopathology and Pharmacology
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